In the current edition of Medness Plus, Esha Sehanobish highlights FDA’s approval of Patisiran (Onpattro) to treat polyneuropathy caused by hereditary transthyretin-mediated amyloidosis. It is the first targeted RNA-based gene therapy to be approved in the United States. Also check out the details of Amicus Therapeutics receiving US approval for Fabry’s disease drug MD Linx and Orilissa emerging as a newest alternative for women with Endometriosis pain. In addition, Shionogi’s Mulpleta garners FDA approval for thrombocytopaenia due to chronic liver disease. The infographics include a summary of the global RNA Therapeutics market and the facts about endometriosis.
FDA approves the first treatment for the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adult patients.
FDA recently approved Onpattro (patisiran) infusion as a treatment for polyneuropathy (peripheral nerve disease). In adults, it is caused by hereditary transthyretin-mediated amyloidosis (hATTR) [1]. hATTR is a rare and often fatal genetic disease that is characterized by the accumulation of abnormal amyloid protein in peripheral nerved, heart and other organs and this is the first FDA approved treatment of hATTR. Another significant outcome is that it is also the first FDA approval of drugs that are based on siRNA (small interfering ribonucleic acid) treatment. The approval was given to Alnylam Pharmaceuticals, Inc. This application was granted Fast Track, breakthrough therapy and fast track review designations by the FDA.
#FDAapproves new treatment for peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR): https://t.co/tMPQItX92w. pic.twitter.com/LnGLIAhhxB
— FDA Drug Information (@FDA_Drug_Info) August 10, 2018
Onpattro, the drug by Alnylam, is a small RNA molecule that is delivered to the liver by a lipid nanoparticle, in an infusion treatment, that functions by interfering with the RNA production of an abnormal form of the transthyretin (TTR) protein thus preventing the accumulation of amyloids in the peripheral nerves and other organs. This belongs to the new class of siRNA drugs that work by silencing a section of the RNA that is involved in causing the disease. The trial consisted of 225 patients. Out of these, 148 of them were randomly assigned to receive Onpattro infusions once every week for 18 months. The remaining 77 received a placebo infusion at the same dosage. A better result was obtained for the polyneuropathy symptoms including muscle strength, reflexes and autonomous symptoms like heart rate, blood pressure for the drug in comparison to the placebo infusions. Before the trial, all patients were given corticosteroids, acetaminophen and antihistamines to reduce the infusion-related effects. The most common adverse reactions to the treatment were nausea, back pain, flushing and headache. Sometimes vision problems such as blurry vision, dry eyes, etc. were also experienced. Now, Onpattro’s average list price minus the rebates to insurers is $450000 per year, per patient. The average net price including the rebates is 345000 per year.
“This approval is part of a broader wave of advances that allow us to treat disease by actually targeting the root cause, enabling us to arrest or reverse a condition, rather than only being able to slow its progression or treat its symptoms. In this case, the effects of the disease cause a degeneration of the nerves, which can manifest in pain, weakness and loss of mobility,” said FDA Commissioner Scott Gottlieb, M.D.
From Visually.
FDA approves a new treatment for Fabry’s disease by Amicus Therapeutics.
FDA recently approved Galafold (migalastat), the first oral medication for Fabry disease in adults. The adults who have genetic mutations that have been determined to be responsive to treatment with Galafold based on clinical trial data are the ones that are indicated to be treated by the drug [2]. The drug is a product of Amicus Therapeutics. This comes after a long-drawn effort by the company to get the approval. It experienced significant setbacks in 2012 and 2016 with insufficient evidence for long- term effects in their clinical trials.
Founder & President of the National Fabry Disease Foundation @JerryWalter on last week’s #FDAApproval and the need for treatment options for people living with #FabryDisease @FabryDisease1 #RareDisease pic.twitter.com/uufqCN8YcI
— Amicus Therapeutics (@amicusrx1) August 14, 2018
The trial was a six-month, placebo-controlled clinical trial conducted in 45 adults with Fabry disease. The patients treated with Galafold showed a reduced globotriaosylceramide in blood vessels of the kidney when compared to the placebo-treated ones. A total of 139 patients were involved in four clinical trials for determining the safety of the drug. The approval came under the Accelerated approval pathway. According to this pathway, FDA may approve drugs under circumstances where it has shown certain potential to address an unmet medical need and has also shown to be clinically beneficial to patients. Further studies need to be conducted in the form of a confirmatory clinical trial for Fabry disease in adults treated with Galafold. It has also been granted Priority Review, under which the FDA will act on the application of the drug within six months of the filling. It also received the status of Orphan Drug status which provides an incentive to assist the development of newer drugs for the treatment of rare diseases. Fabry’s disease is a genetic disorder that is caused by mutations in α-galactosidase A(GLA) gene on the X-chromosome. It results in the accumulation of globotriaosylceramide (GL-3) in kidney, blood vessels, the heart, nerves and other organs. It is rare but affects both males and females. Fabry disease leads to slow and progressive kidney disease, cardiac hypertrophy, arrhythmia, stroke and early death. Headache, nasal and throat irritation, nausea, urinary tract infection and fever are some of the adverse effects associated with this drug treatment.
“Thus far, treatment of Fabry disease has involved replacing the missing enzyme that causes the particular type of fat buildup in this disease. Galafold differs from enzyme replacement in that it increases the activity of the body’s deficient enzyme,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research.
FDA approves the ORILISSA (elagolix) from Abbvie for the management of moderate to severe pain associated with Endometriosis.
FDA recently announced the approval of ORILISSA (elagolix), the first and only gonadotropin-releasing hormone antagonist that has been developed by Abbvie in cooperation with Neurocrine Biosciences, Inc [3]. The primary aim of this drug is to provide relief to women who experience moderate to severe endometriosis pain. This was released under Priority Review and will be available in the pharmacies in US in early August 2018.
New Post: Gynecologists Praise Orilissa as Newest Alternative for Women with Endo Pain https://t.co/FhZVquJaYt pic.twitter.com/JgDJcQot9v
— Endometriosis News (@endometriosis24) August 10, 2018
Endometriosis is a very common gynecologic problem in the US and it is characterized by chronic pelvic pain. It is often managed using oral contraceptives, nonsteroidal anti-inflammatory drugs (NSAIDs), hormonal therapy and opioids. In more severe cases surgical procedures such as laparotomy, laparoscopy or hysterectomy are performed, but they might not cure the patient. ORILISSA is a nonpeptide small molecule gonadotropin-releasing hormone receptor antagonist that binds to the receptor and inhibits the signaling pathway, competitively. This results in a dose-dependent suppression of Follicle stimulating hormone (FSH) and Luteinizing hormone (LH) which eventually leads to a decrease in the blood concentrations of ovarian sex hormones, progesterone and estradiol. 1700 women with moderate to severe endometriosis were investigated in the form of the largest endometriosis Phase 3 study program. Based on the data there was a reduction in menstrual pelvic pain and non-menstrual pelvic pain. There was a higher response in women who were treated with ORILISSA 150 mg once daily and 200 mg twice daily for the same symptoms when compared to the effects of the placebo. Responders were those who showed a reduction in the daily menstrual and non-menstrual pain upon treatment without any increase in analgesic use (NSAIDs) for endometriosis-associated pain. The recommended dose and duration of usage is up to 24 months for 150 mg once daily dose and up to six months for 200 mg twice daily dose. There is a dose-dependent decrease in bone mineral density (BMD). The BMD loss increases with increase in the duration of use and may not be completely reversible when the treatment is stopped. ORILISSA has been recommended to be taken orally at the same time each day with or without food.
“ORILISSA represents a significant advancement for women with endometriosis and physicians who need more options for the medical management of this disease. The approval of ORILISSA demonstrates AbbVie’s continued commitment to address serious diseases and unmet needs,” said Michael Severino, M.D., Executive Vice President, Research and Development and Chief Scientific Officer, AbbVie.
From Visually.
FDA announces approval of Mulpleta from Shionogi for treatment of Thrombocytopenia in adults.
Shionogi a major research-driven biopharmaceuticals company recently announced the FDA approval of Mulpleta (lusutrombopag) after completing a Priority Review for its effectiveness in treating thrombocytopenia in adults with chronic liver disease and are scheduled to undergo a procedure [4].
This was based on consistent safety and efficacy data obtained from two Phase 3 clinical trials, L-PLUS 1 and L-PLUS 2. In each of these Mulpleta met the primary and secondary endpoints with statistical significance.
The US Food and Drug Administration (FDA) has approved lusutrombopag (Mulpleta, Shionogi Inc) for the treatment of thrombocytopenia in adults with chronic liver disease who are scheduled to undergo a medical or dental procedure. https://t.co/IIuq30BUwZ pic.twitter.com/QSEKysxbSQ
— PDSA ITP SUPPORT (@PDSA_ITP) August 1, 2018
A common complication of chronic liver disease is thrombocytopenia which could be caused due to a decrease in thrombopoietin amongst other factors. It is usually characterized by a platelet count of less than 150,000/μL and occurs in 78% patients with cirrhosis. Often these patients are at an increased risk of bleeding, frequent hospital visits, platelet transfusions in comparison to those that have chronic liver disease but without thrombocytopenia. Even the annual health care cost for the patients with thrombocytopenia is higher than those without it. Sometimes in severe cases, there might be further complications that result in a delayed or canceled treatment. Mulpleta (lusutrombopag) is a small molecule thrombopoietin receptor antagonist that interacts with the transmembrane domain of human TPO receptors that are expressed on megakaryocytes to induce the differentiation and proliferation of these megakaryocytic progenitor cells. It is a once-daily, orally administered drug given to normalize the platelet counts. The only known and common adverse effect of this drug is a headache. “We are very pleased the FDA has approved Mulpleta as a new, safe and effective treatment,” said Takayuki Yoshioka, President and Chief Executive Officer, Shionogi Inc. “This new therapy offers physicians and patients another choice beyond platelet transfusions as adult patients with CLD often undergo procedures that could put them at increased risk for bleeding.”
Akouos raises $50 million to support genetic therapies that restore and preserve hearing
Akouos, a precision genetic medicine company that specializes in developing gene therapies to preserve and restore hearing, recently announced that they have raised $50 million in Series A financing [5]. Proceeds from this new influx of finance will allow the company to carry and make advancements in their first-in-human clinical studies. It will also allow them to proceed with their other projects which are in the pipeline such as the ones that are involved in addressing sensorineural hearing with gene targets.
Akouos scores $50M Series A for gene therapy in hearing loss https://t.co/yLfDyfvp5c pic.twitter.com/s3G3E4fJlC
— Swedish Biotech (@BiotechSweden) August 16, 2018
The company uses targeted adeno-associated viral vector (AAV) based gene therapy for sensorineural hearing loss which mainly arises from damage to sensory cells and/or nerve fibers of the inner ear. It is one of the most common forms of hearing loss that seems to affect newborns and a quarter of adults over the age of 65. Akouos also focusses on defects caused due to genetic mutations. The round was co-led by seed investors 5AM Ventures and New Enterprise Associates. They were joined by the already existing seed investor Partners Innovation Fund and new investors RA Capital Management, Novartis Venture Fund and Sofinnova Ventures.
“Hearing loss is one of the greatest challenges in medicine today, and with no FDA-approved therapies available, an area of severe unmet need. Akouos has a unique opportunity to bring forward the world’s first precision medicines for individuals with genetically-driven forms of hearing loss. The expansion of our team and investor base, in addition to our founding partnerships with Massachusetts Eye and Ear and Lonza, puts us in a strong position to advance the clinical studies that will convert the promise of our approach into meaningful therapies,” said Manny Simons, Ph.D., founder and CEO of Akouos.
Magnolia Neurosciences Corporation receives $31 million in Series A funding to develop targeted neuroprotective therapies
Accelerator Life Science Partners, a life science investment and management firm, recently announced that they were instrumental in launching Magnolia Neurosciences Corporation, a company that will focus on developing newer classes of neuroprotective medicine [6]. This was done in collaboration with The University of Texas MD Anderson Cancer Center and the company will advance the discoveries made by the researchers in MD Anderson’s Therapeutic Discovery division and the Neurodegeneration Consortium (NDC). Magnolia Neurosciences was launched with $31 million on the form of Series A investment by Accelerator. The participants in the $31 million series A venture include AbbVie Ventures, Alexandria Venture Investments, ARCH Venture Partners, Eli Lilly and Company, Innovate NY Fund, Johnson & Johnson Innovation – JJDC, Inc., the Partnership Fund for New York City, Pfizer Ventures, Watson Fund, L.P., WuXi AppTec’s Corporate Venture Fund and 180 Degree Capital Corp.
#JJDC is proud to announce its investment in Magnolia Neurosciences Corporation, a recently launched company developing innovative medicines for patients suffering from a variety of #neurodegenerative disorders. Learn more here: https://t.co/TTfKYs8ULP pic.twitter.com/UCwpVsaXcF
— JNJ Innovation (@JNJInnovation) August 14, 2018
Accelerator is known to help in the development and the commercialization of breakthrough biotechnology discoveries. It partners various companies by consulting and assisting them in all stages of their development by giving them the best chance for long-term success. Magnolia, on the other hand, was developed to focus mainly on different classes of neuroprotective medicine since neurodegenerative diseases affect millions of people in the US. Excess neurons are known to be eliminated by programmed cell death, during embryonic development. In case of Alzheimer’s disease, some of these tightly controlled processes get re-activated leading to neuronal damage. Thus, blocking specific components might lead to the preservation of brain tissues and drugs need to be designed keeping this in mind. Hence the development of a new company to do the same will be extremely beneficial since they will be supported by authentic clinical data from MD Anderson.
“There is a critical need to develop medicines that slow or stop neuronal loss in these patients, and a growing body of data suggests that inhibition of these specific pathways has the potential to preserve neuron viability across a variety of disease states and pathological conditions,” said Jim Ray, PhD, director of Neurodegeneration Consortium. “Magnolia Neurosciences is focused on developing potent and highly selective neuroprotective therapies that have compelling preclinical pharmacologic profiles and for which clinical proof of concept can be obtained rapidly to address significant unmet patient needs.”
References:
- https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm616518.htm.
- https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm616598.htm.
- https://news.abbvie.com/news/press-releases/abbvie-receives-us-fda-approval-orilissa-elagolix-for-management-moderate-to-severe-pain-associated-with-endometriosis.htm.
- https://www.businesswire.com/news/home/20180801005551/en/Shionogi-Announces-FDA-Approval-Mulpleta%C2%AE-Lusutrombopag.
- https://www.businesswire.com/news/home/20180807005074/en/Akouos-Raises-50-Million-Series-Financing-Expands.
- https://www.businesswire.com/news/home/20180813005133/en/Accelerator-Life-Science-Partners-Launches-Magnolia-Neurosciences.
About the Author:
Esha Sehanobish
She is presently a Postdoctoral research fellow at Albert Einstein college of medicine, NY and works on characterization of enzymes that could act as potential therapeutic targets against tuberculosis. She is an enzymologist with a doctoral degree from the University of Central Florida in 2016. She loves using her communication skills to raise awareness about the importance of science in general by using social media. When she is not doing “science”, she loves designing and painting as a way of expressing ones thoughts through graphics and color.
Editor and Blog Design
Abhi graduated from the Molecular Biophysics Unit of IISc (Bangalore, India) in 2011. As a Biomedical Scientist, he has worked with all three life-forms in his 13-year research career, viz., particulate, unicellular and multicellular. He is currently an Assistant Scientist at Emory University (Atlanta, GA) studying mechanisms of tumor recurrence in kids with brain tumors. As a postdoctoral fellow, he was the recipient of two Young Investigator Awards from Alex Lemonade Stand Foundation (Philadelphia, PA) and Rockland Immunochemicals. His current research has been funded by Northwestern Mutual Foundation (Milwaukee, WI), CURE Childhood Cancer Foundation (Atlanta, GA) and American Association for Cancer Research (AACR). When he is not on the bench you will find him spending time with his family or exploring the world through traveling and blogging.
Cover image: (Cell Image Library)Fluorescent image of serum starved fibroblasts created from four images stitched together. Image shows the microtubules (green) and nucleus (red). Ninth Prize, 2007 Olympus BioScapes Digital Imaging Competition.
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